4.1 Microfluidics Systems
Over the past several years researchers have made advances in microfluidics based upon manipulation of individual droplets through direct electrical control. Examples of such systems can be found in U.S. Pat. No. 6,911,132 and U.S. Patent Application Publication No. 2004/0058450, both to Pamula et al. These patent documents describe an apparatus for electrically manipulating droplets. Wixforth, U.S. Pat. No. 6,777,245, assigned to Advalytix AG (Munich) has described a technology that is reported to have the capability to electronically control chemical reactions on the surface of a biochip using surface acoustic waves generated by applying radio-frequency electric pulses to the chips. Gascoyne and others in U.S. Patent Publications 2005/0072677, 2004/0178068, 2004/0011651, 2003/0173223, 2003/0171325, 2003/0102854, and 2002/0036139, have reported the use of dielectrophoresis to manage the movement of a material or an object through a body of fluid. Patents and patent publications assigned to Fluidigm have described a technology based on fluid-control valves and interconnected channels that form networks of discrete pathways and intermediate switches. Labcyte Inc., U.S. Pat. No. 6,416,164 and other patents, describes the use of focused acoustic energy (ultrasound) to eject small droplets of liquid from open wells for its products that target sub-microliter transfer volumes. HandyLab has reported the development of a microfluidic system that relies on internally generated pressure—thermo-pneumatic pumps—to create and propel nanoliter-sized liquid plugs through a micro-channel network in which multiple discrete plugs function independently of each other. There remains a need in the art for systems that can be used to directly control these droplet microactuators, systems that can be used to develop and troubleshoot software for controlling droplet microactuators, and software languages for controlling droplet microactuators and components of droplet microactuator systems.
Microfluidic systems can be broadly categorized into continuous-flow and discrete-flow based architectures. Continuous-flow systems rely on liquid that is continually fed into the system (think of pipes, pumps, and valves), whereas discrete-flow systems utilize droplets of liquid.
Continuous flow systems are limited by the fact that liquid transport is physically confined to permanently etched channels. The transport mechanisms used are usually pressure-driven by external pumps or electrokinetically-driven by high-voltages. These approaches involve complex channeling and require large supporting systems in the form of external pumps, valves and power supplies. These restrictions make it difficult to achieve high degrees of functional integration and control in conventional continuous-flow systems, particularly in realizing a handheld device at the point of sample collection. Moreover, the fluid flow is unidirectional and therefore is not easily reconfigurable or programmable.
In addition, the technological limitations of continuous-flow channel systems do not allow the integration of multiple formats of analysis such as PCR, immunoassays, chemistry, and cell handling together onto a single chip. Even where these technologies miniaturize the assay on a lab-on-a-chip they require a large instrument to manage even limited operations on the chip. Therefore, a need exists for a microfluidic lab-on-a-chip that can meet the needs of multifunctionality and portability demanded by POSC applications.
4.2 Portable Analyzer Background
Point of sample collection testing is useful in a wide variety of contexts, from medical monitoring and diagnostics to environmental testing. In contexts, like medical monitoring or environmental monitoring of effluent streams, point of sample testing can minimize the time from sample collection to action taken. Moreover, in many instances it may be virtually impossible to preserve samples for transport to a central lab. Even when such preservation is possible, the extensive procedures required may render preservation and transport to a central lab economically unfeasible. Alternatively, researchers may be forced to accept some diminishment in accuracy of analysis caused by transport under less than ideal conditions.
Several groups have made or attempted to make systems that permit point of sample collection testing. For example, Lauks, U.S. Pat. No. 5,096,669, describes a sensing device for real time fluid analysis. Zelin, U.S. Pat. No. 5,821,399, describes a method for automatic fluid flow compensation in a disposable fluid analysis sensing device. In U.S. Pat. No. 5,124,661, Zelin et al. describe a reusable test unit for testing the functionality of a portable blood analyzer. Enzer et al., U.S. Pat. No. 4,436,610, describes an apparatus for measuring the hydrogen ion activity or pH value of blood. Cheng et al., U.S. Pat. Nos. 6,071,394, 6,403,367 and 6,280,590, and Sheldon et al., U.S. Pat. No. 6,129,828, all assigned to Nanogen Inc. (San Diego, Calif.), describe a device to perform separation of bacterial and cancer cells from peripheral human blood in microfabricated electronic chips by dielectrophoresis. Miles et al., U.S. Pat. No. 6,576,459, describes a sample preparation and analysis device which incorporates both immunoassays and PCR assays into a compact microchip. Biosite Inc. (San Diego, Calif.) sells a point-of-care testing product for a set of three immunoassays for detection of elevated cardiac markers related to heart attack (myoglobin, CK-MB, and troponin I) (http://www.biosite.com/products/cardio.aspx). Buechler et al., U.S. Pat. No. 6,074,616, describes a fluorometer with drive electronics for positioning the sample with respect to the optical components. Brennen et al., U.S. Pat. No. 6,632,400, describes a microfluidic device consisting of microfluidic channels, compartments, and flow control elements. Boecker et al., U.S. Pat. No. 6,966,880, describes a portable medical analyzer with a sampling module with integrated sample extraction device, a sample port for receiving body fluid, an assay sensor module for analysis of the body fluid, an analytical detector module with detection of information from the assay, and a communications module for transferring the information to a remote location via a wired or wireless network.